Characterization of WAGR Syndrome and Other Chromosome 11 Gene Deletions
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Purpose
This study will explore conditions caused by the absence of certain genes on chromosome 11. These conditions include WAGR syndrome, which is characterized by a kidney tumor called Wilm's tumor, aniridia (absence of the iris of the eye), genital and urinary abnormalities, mental retardation, and possibly other symptoms. This study will examine how the genes on chromosome 11 affect people and whether the absence of specific genes is associated with specific symptoms.
Healthy normal volunteers, people with isolated aniridia, and people with WAGR or another chromosome 11 gene deletion may be eligible for this study. Participants must be at least 6 years old. Parents of patients may also participate for genetic studies.
Participants undergo some or all of the following procedures, depending on whether they are a child, adult, healthy volunteer or parent of a patient:
- Medical history and physical examination, eye examination, blood, urine and saliva tests, electrocardiogram (EKG) and electroencephalogram (EEG)
- X-rays, scans and other tests to measure body composition (fat, muscle and bone development and thickness) and MRI to examine the eyes and the brain and to measure abdominal fat
- Ultrasound studies of the kidneys, ovaries and uterus (in females) and testes (in males)
- Meal tests, food diaries and food preference tests
- Questionnaires about eating and sleep habits, personality and character traits and responses to pain and injury
- Neuropsychological tests
- Tests of resting metabolic rate, energy expenditure and glucose (sugar) tolerance
- Hot and cold sensitivity tests, vibration sensitivity test, cold tolerance test and smell identification test
- Eye and hearing tests
- Nerve conduction studies and study of sensory information conduction from peripheral nerves to the spinal cord and brain
- Computer photography
- Evaluation by sub-specialists (e.g., endocrinologist, ophthalmologist, physiatrist, neurologist or others) as indicated by the patient's medical history and test results
| Condition |
|---|
|
WAGR Syndrome Wilm's Tumor Aniridia Urogenital Abnormalities Mental Retardation |
| Study Type: | Observational |
| Official Title: | WAGR Syndrome and Other 11p Contiguous Gene Deletions: Clinical Characterization and Correlation With Genotype |
| Estimated Enrollment: | 375 |
| Study Start Date: | September 2008 |
WAGR syndrome is a rare genetic disorder characterized by Wilms tumor, aniridia, genitourinary anomalies and mental retardation. The syndrome is caused by heterozygous contiguous gene deletions of variable size on chromosome 11, involving a region that encompasses more than 100 genes, many of which have unknown function in humans. In our preliminary studies, we have observed that approximately two-thirds of patients with WAGR syndrome have deletion of the gene which encodes brain-derived neurotrophic factor (BDNF), and that BDNF haploinsufficiency is associated with obesity and with parent reports of hyperphagia and impaired nociception, suggesting that BDNF may play an important role in human energy balance as well as pain sensation. We now propose to conduct a comprehensive clinical phenotype-genotype study on patients with WAGR syndrome and other 11p deletions. We plan to enroll 75 subjects with WAGR syndrome/11p deletions who will undergo evaluations of the following systems: metabolic/endocrine, sensation/nociception, ophthalmologic, audiologic, neurocognitive, renal/genitourinary, oncologic, dental/craniofacial, cardiac, and orthopedic. Genetic testing will be performed on the parents of subjects with WAGR syndrome/11p deletion who choose to participate in order to determine if parental origin of the deletion influences phenotype. We also plan to enroll 75 healthy subjects as body-size matched controls for metabolic studies and 75 patients with isolated aniridia as visually impaired controls for neurocognitive studies. We hypothesize that a more complete understanding of the correlation between phenotype and genotype could lead to improved medical care of these patients through genotype-specific management as well as yield further insight into the physiological role of genes in the 11p region.
Eligibility| Ages Eligible for Study: | 2 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
- INCLUSION CRITERIA:
For WAGR/11p deletion subjects:
- Diagnosis of WAGR/11p deletion confirmed by prior genetic testing or clinical history consistent with WAGR syndrome (Wilms Tumor and/or genitourinary anomalies plus aniridia). Genetic diagnosis will be confirmed at the NIH, if not done previously
- Age greater than or equal to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight < 12 kg) blood draw, eye examination, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
- Medically stable (so that the patient can safely undergo planned testing); if history of Wilms tumor, must be > 6 months since completion of chemotherapy and must be considered in remission by primary oncologist caring for the patient
For parents of WAGR/11p deletion subjects:
a)Biological parent of child with WAGR/11p deletion able to give consent for self participation
For healthy control subjects:
- Age greater than or eqaul to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight < 12 kg) blood draw, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
- No chronic medications. Use of as-needed and over-the-counter medications will be reviewed on a case-by-case basis by the Principal Investigator
- No chronic medical or psychiatric conditions anticipated to affect results or impede study participation
For aniridia subjects:
- Diagnosis of aniridia confirmed by ophthalmologist
- Age greater than or eqaul to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight < 12 kg) blood draw, eye examination, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
- Medically stable, with no chronic medical or psychiatric conditions anticipated to affect results or impede study participation
EXCLUSION CRITERIA:
For WAGR/11p deletion subjects:
- Anorexiant use in preceding 6 months
- Greater than 2% body weight loss in preceding 6 months
- Pregnancy
- Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study
For parents of WAGR/11p deletion subjects:
a) No exclusions other than lack of ability to give consent for participation
For healthy control subjects:
- Anorexiant use in preceding 6 months
- Greater than 2% body weight loss in preceding 6 months
- Pregnancy
- Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study
For aniridia subjects:
- Anorexiant use in preceding 6 months
- Greater than 2% body weight loss in preceding 6 months
- Pregnancy
- Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study
Contacts and Locations| Contact: Joan C Han, M.D. | (301) 435-7820 | hanjo@mail.nih.gov |
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 prpl@mail.cc.nih.gov | |
| Principal Investigator: | Joan C Han, M.D. | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
More Information
Additional Information:
Publications:
| ClinicalTrials.gov Identifier: | NCT00758108 History of Changes |
| Other Study ID Numbers: | 080213, 08-CH-0213 |
| Study First Received: | September 20, 2008 |
| Last Updated: | May 1, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institutes of Health Clinical Center (CC):
|
Genotype/Phenotype Correlation Energy Homeostasis Nociception Obesity Behavior and Neurocognition WAGR Syndrome |
Wilm's Tumor Aniridia Mental Retardation Urogenital Abnormalities Healthy Volunteer |
Additional relevant MeSH terms:
|
Congenital Abnormalities Aniridia Mental Retardation Wilms Tumor Urogenital Abnormalities WAGR Syndrome Eye Abnormalities Eye Diseases Eye Diseases, Hereditary Iris Diseases Uveal Diseases Genetic Diseases, Inborn Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases |
Signs and Symptoms Mental Disorders Diagnosed in Childhood Mental Disorders Neoplasms, Complex and Mixed Neoplasms by Histologic Type Neoplasms Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Neoplastic Syndromes, Hereditary Kidney Diseases Urologic Diseases 46, XY Disorders of Sex Development Disorders of Sex Development |
ClinicalTrials.gov processed this record on May 23, 2013